The Advances of Thyroid Cancer's Molecular Diagnosis and Treatment_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGHai-bing , ZHUQing ,  YANGGuang-lun

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;

Corresponding author：

YANGGuang-lun, Email: guanglunyang@163.com

Keywords：

Thyroid cancer; Molecular diagnosis and treatment; Review

DOI：

10.7507/1007-9424.20160031

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the progress in the diagnosis and treatment of thyroid cancer related genes. Methods By using the method of literature review, The literatures of thyroid cancer related gene were reviewed on the study of emerging diagnosis and treatment strategy. Results Combined detection of BRAF oncogene, RAS oncogene, RET/PTC rearrangement, PAX8-PPAR_γ fusion gene and its related genes, can effectively improve the prediction accuracy of the malignant thyroid nodule form benign, and has become a basis of targeted drug therapy. Conclusion In preoperative thyroid cancer, Joint detection of related gene can provide a molecular basis for the patients to guide the operation and drug treatment.

Citation： YANGHai-bing, ZHUQing, YANGGuang-lun. The Advances of Thyroid Cancer's Molecular Diagnosis and Treatment. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(1): 109-113. doi: 10.7507/1007-9424.20160031 Copy

1.	McNeil C. Annual cancer statistics report raises key questions. J Natl Cancer Inst, 2006, 98(22):1598-1599.
2.	孙嘉伟,许晓君,蔡秋茂, 等. 中国甲状腺癌发病趋势分析. 中国肿瘤, 2013, 22(9):690-693.
3.	Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet, 2013, 381(9871):1058-1069.
4.	Omur O, Baran Y. An update on molecular biology of thyroid cancers. Crit Rev Oncol Hematol, 2014, 90(3):233-252.
5.	Nikiforov YE. Thyroid carcinoma:molecular pathways and thera-peutic targets. Mod Pathol, 2008, 21 Suppl 2:S37-S43.
6.	Smith N, Nucera C. Personalized therapy in patients with anaplasti-cthyroid cancer:targeting genetic and epigeneticalterations. J Clin Endocrinol Metab, 2015, 100(1):35-42.
7.	Duman BB, Kara OI, Uğuz A, et al. Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma. Contemp Oncol (Pozn), 2014, 18(4):234-240.
8.	Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol, 2011, 7(10):569-580.
9.	Perincheri S, Hui P. KRAS mutation testing in clinical practice. Expert Rev Mol Diag, 2015, 15(3):375-384.
10.	Alonso-Gordoa T, Díez JJ, Durán M, et al. Advances in thyroid cancer treatment:latest evidence and clinical potential. Ther Adv Med Oncol, 2015, 7(1):22-38.
11.	Bentzien F, Zuzow M, Heald N, et al. In Vitro and In Vivo activity of cabozantinib (XL184):an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer. Thyroid. 2013, 23(12):1569-1577.
12.	Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusiono-ncogene in human thyroid carcinoma. Science, 2000, 289(5483):1357-1360.
13.	Wang Y, Hou P, Yu H, et al. High prevalence and mutual exclusivity ofgenetic alterations in the phosohatidiylinositol-3-kinase/Akt pathwayin thyroid tumors. J Clin Endocrinol Metab, 2007, 92(6):2387-2390.
14.	Reddi HV, McIver B, Grebe SK, et al. The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene inthyroid tumori-genesis. Endocrinology, 2007, 148(3):932-935.
15.	Omur O, Baran Y. An update onmolecular biology of thyroid cancers. Crit Rev OncolHematol, 2014, 90(3):233-252.
16.	Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF^V600E mutation and mortality in patients with papillarythyroid cancer. JAMA, 2013, 309(14):1493-1501.
17.	Kim SW, Lee JI, Kim JW, et al. BRAF^V600E mutation analysis infine-needle aspiration cytology specimens for evaluation of thyroidno-dule:a large series in a BRAF^V600E-prevalent population. J ClinEn-docrinol Metab, 2010, 95(8):3693-3700.
18.	Li C, Lee KC, Schneider EB, et al. BRAF^V600E mutation and its association withclinicopathological features of papillary thyroid cancer:ameta-analysis. J Clin Endocrinol Metab, 2012, 97(12):4559-4570.
19.	Nikiforov YE. Molecular analysis of thyroid tumors. Mod Pathol, 2011, Suppl 24:S34-S43.
20.	Michaele J, Armstrong, Huaitao Yang, et al. PAX8/PPARc rearran-gement in thyroid nodules predicts follicular-pattern carcinomas, in particularthe encapsulated follicular variant of papillary carcinoma. Thyroid Cancer And Nodules, 2014, 24(9):1369-1374.
21.	Fagin JA. Challenging dogma in thyroid cancer moleculargenetics-role of RET/PTC and BRAF in tumor initiation. J ClinEndocrinol Metab, 2004, 89(9):4264-4266.
22.	Leeman-Neill RJ, Brenner AV, Little MP, et al. RET/PTC and PAX8/PPAR_γ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics. Cancer, 2013, 119(10):1792-1799.
23.	Hsiao SJ, Nikiforov YE. Molecular approaches to thyroid cancer diagnosis. Endocr Relat Cancer, 2014, 21(5):T301-T313.
24.	Guerra A, Zeppa P, Bifulco M, et al. Concomitant BRAF^V600E mutation and RET/PTCRe arrangement is a frequent occurrence inpapillary thyroid carcinoma. Thyroid, 2014, 24(2):254-259.
25.	Nikiforova MN, Chiosea SI, Nikiforov YE. MicroRNA expression-profiles in thyroid tumors. Endocr Pathol, 2009, 20(2):85-91.
26.	Fallahi P, Ferrari SM, Santini F, et al. Sorafenib and thyroid cancer. BioDrugs, 2013, 27(6):615-628.
27.	Salvatore G, De Falco V, Salerno P, et al. BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res, 2006, 12(5):1623-1629.
28.	Thomas L, Lai SY, Dong W, et al. Sorafenib in metastatic thyroid cancer:a systematic review. Oncologist, 2014, 19(3):251-258.
29.	Savvides P, Nagaiah G, Lavertu P, et al. Phase Ⅱ trial of sorafenib in patients with advanced anaplasticcarcinoma of the thyroid. Thyroid, 2013, 23(5):600-604.
30.	Nehs MA, Nucera C, Nagarkatti SS, et al. Late intervention with anti-BRAF^V600E therapyinduces tumor regression in an orthotopic mouse model of humananaplastic thyroid cancer. Endocrinology, 2012, 153(2):985-994.
31.	Ostrem JM, Peters U, Sos ML, et al. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature, 2013, 503(7477):548-551.
32.	Baker R, Lewis SM, Sasaki AT, et al. Sitespecific monoubiquitination activates Ras by impeding GTPase-activating protein function. Nat Struct Mol Biol, 2013, 20(1):46-52.
33.	Borrello MG, Ardini E, Locati LD, et al. RET inhibition:Implications in cancer therapy. Expert Opin Ther Targets, 2013, 17(4):403-419.
34.	Wells SA, Robinson BG, Gagel RF, et al. Vandetanib inpatients with locally advanced or metastatic medullary thyroid cancer:A randomized, double-blind phase Ⅲ trial. J Clin Oncol, 2012, 30(2):134-141.
35.	Carlomagno F, Guida T, Anaganti S, et al. Disease associated muta-tions at valine 804 in the RET receptor tyrosine kinase conferresis-tance to selective kinase inhibitors. Oncogene, 2004, 23(36):6056-6063.
36.	Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastaticdifferentiated thyroid cancer:a randomised, double-blind, phase 2 trial. Lancet Oncol, 2012, 13(9):897-905.
37.	Kim DW, Jo YS, Jung HS, et al. An orally administered multitar-get tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J ClinEndocr Metab, 2006, 91(10):4070-4076.
38.	Ruan M1, Liu M, Dong Q, et al. Iodide-and glucose-handling gene expression regulated by sorafenib or cabozantinib in papillary thyroid cancer. J Clin Endocrinol Metab, 2015, 100(5):1771-1779.
39.	Alao JP, Michlikova S, Dinér P, et al. Selective inhibition of RET mediated cell proliferation in vitro by the kinase inhibitor SPP86. BMC Cancer, 2014, 14:853.
40.	Placzkowski KA, Reddi HV, Grebe SK, et al. The role of the PAX8/PPARgamma fusion oncogene in thyroid cancer. PPAR Res, 2008, 2008:672829.
41.	Uitdehaag JC, de Roos JA, van Doornmalen AM,et al. Selective targeting of CTNBB1-, KRAS- or MYC-driven cell growth by combinations of existing drugs. PLoS One, 2015, 10(5):e0125021.
42.	Safa AR, Saadatzadeh MR, Cohen-Gadol AA, et al. Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs. Genes Dis, 2015, 2(2):152-163.

1. McNeil C. Annual cancer statistics report raises key questions. J Natl Cancer Inst, 2006, 98(22):1598-1599.
2. 孙嘉伟,许晓君,蔡秋茂, 等. 中国甲状腺癌发病趋势分析. 中国肿瘤, 2013, 22(9):690-693.
3. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet, 2013, 381(9871):1058-1069.
4. Omur O, Baran Y. An update on molecular biology of thyroid cancers. Crit Rev Oncol Hematol, 2014, 90(3):233-252.
5. Nikiforov YE. Thyroid carcinoma:molecular pathways and thera-peutic targets. Mod Pathol, 2008, 21 Suppl 2:S37-S43.
6. Smith N, Nucera C. Personalized therapy in patients with anaplasti-cthyroid cancer:targeting genetic and epigeneticalterations. J Clin Endocrinol Metab, 2015, 100(1):35-42.
7. Duman BB, Kara OI, Uğuz A, et al. Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma. Contemp Oncol (Pozn), 2014, 18(4):234-240.
8. Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol, 2011, 7(10):569-580.
9. Perincheri S, Hui P. KRAS mutation testing in clinical practice. Expert Rev Mol Diag, 2015, 15(3):375-384.
10. Alonso-Gordoa T, Díez JJ, Durán M, et al. Advances in thyroid cancer treatment:latest evidence and clinical potential. Ther Adv Med Oncol, 2015, 7(1):22-38.
11. Bentzien F, Zuzow M, Heald N, et al. In Vitro and In Vivo activity of cabozantinib (XL184):an inhibitor of RET, MET, and VEGFR2, in a model of medullary thyroid cancer. Thyroid. 2013, 23(12):1569-1577.
12. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusiono-ncogene in human thyroid carcinoma. Science, 2000, 289(5483):1357-1360.
13. Wang Y, Hou P, Yu H, et al. High prevalence and mutual exclusivity ofgenetic alterations in the phosohatidiylinositol-3-kinase/Akt pathwayin thyroid tumors. J Clin Endocrinol Metab, 2007, 92(6):2387-2390.
14. Reddi HV, McIver B, Grebe SK, et al. The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene inthyroid tumori-genesis. Endocrinology, 2007, 148(3):932-935.
15. Omur O, Baran Y. An update onmolecular biology of thyroid cancers. Crit Rev OncolHematol, 2014, 90(3):233-252.
16. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF^V600E mutation and mortality in patients with papillarythyroid cancer. JAMA, 2013, 309(14):1493-1501.
17. Kim SW, Lee JI, Kim JW, et al. BRAF^V600E mutation analysis infine-needle aspiration cytology specimens for evaluation of thyroidno-dule:a large series in a BRAF^V600E-prevalent population. J ClinEn-docrinol Metab, 2010, 95(8):3693-3700.
18. Li C, Lee KC, Schneider EB, et al. BRAF^V600E mutation and its association withclinicopathological features of papillary thyroid cancer:ameta-analysis. J Clin Endocrinol Metab, 2012, 97(12):4559-4570.
19. Nikiforov YE. Molecular analysis of thyroid tumors. Mod Pathol, 2011, Suppl 24:S34-S43.
20. Michaele J, Armstrong, Huaitao Yang, et al. PAX8/PPARc rearran-gement in thyroid nodules predicts follicular-pattern carcinomas, in particularthe encapsulated follicular variant of papillary carcinoma. Thyroid Cancer And Nodules, 2014, 24(9):1369-1374.
21. Fagin JA. Challenging dogma in thyroid cancer moleculargenetics-role of RET/PTC and BRAF in tumor initiation. J ClinEndocrinol Metab, 2004, 89(9):4264-4266.
22. Leeman-Neill RJ, Brenner AV, Little MP, et al. RET/PTC and PAX8/PPAR_γ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics. Cancer, 2013, 119(10):1792-1799.
23. Hsiao SJ, Nikiforov YE. Molecular approaches to thyroid cancer diagnosis. Endocr Relat Cancer, 2014, 21(5):T301-T313.
24. Guerra A, Zeppa P, Bifulco M, et al. Concomitant BRAF^V600E mutation and RET/PTCRe arrangement is a frequent occurrence inpapillary thyroid carcinoma. Thyroid, 2014, 24(2):254-259.
25. Nikiforova MN, Chiosea SI, Nikiforov YE. MicroRNA expression-profiles in thyroid tumors. Endocr Pathol, 2009, 20(2):85-91.
26. Fallahi P, Ferrari SM, Santini F, et al. Sorafenib and thyroid cancer. BioDrugs, 2013, 27(6):615-628.
27. Salvatore G, De Falco V, Salerno P, et al. BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res, 2006, 12(5):1623-1629.
28. Thomas L, Lai SY, Dong W, et al. Sorafenib in metastatic thyroid cancer:a systematic review. Oncologist, 2014, 19(3):251-258.
29. Savvides P, Nagaiah G, Lavertu P, et al. Phase Ⅱ trial of sorafenib in patients with advanced anaplasticcarcinoma of the thyroid. Thyroid, 2013, 23(5):600-604.
30. Nehs MA, Nucera C, Nagarkatti SS, et al. Late intervention with anti-BRAF^V600E therapyinduces tumor regression in an orthotopic mouse model of humananaplastic thyroid cancer. Endocrinology, 2012, 153(2):985-994.
31. Ostrem JM, Peters U, Sos ML, et al. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature, 2013, 503(7477):548-551.
32. Baker R, Lewis SM, Sasaki AT, et al. Sitespecific monoubiquitination activates Ras by impeding GTPase-activating protein function. Nat Struct Mol Biol, 2013, 20(1):46-52.
33. Borrello MG, Ardini E, Locati LD, et al. RET inhibition:Implications in cancer therapy. Expert Opin Ther Targets, 2013, 17(4):403-419.
34. Wells SA, Robinson BG, Gagel RF, et al. Vandetanib inpatients with locally advanced or metastatic medullary thyroid cancer:A randomized, double-blind phase Ⅲ trial. J Clin Oncol, 2012, 30(2):134-141.
35. Carlomagno F, Guida T, Anaganti S, et al. Disease associated muta-tions at valine 804 in the RET receptor tyrosine kinase conferresis-tance to selective kinase inhibitors. Oncogene, 2004, 23(36):6056-6063.
36. Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastaticdifferentiated thyroid cancer:a randomised, double-blind, phase 2 trial. Lancet Oncol, 2012, 13(9):897-905.
37. Kim DW, Jo YS, Jung HS, et al. An orally administered multitar-get tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J ClinEndocr Metab, 2006, 91(10):4070-4076.
38. Ruan M1, Liu M, Dong Q, et al. Iodide-and glucose-handling gene expression regulated by sorafenib or cabozantinib in papillary thyroid cancer. J Clin Endocrinol Metab, 2015, 100(5):1771-1779.
39. Alao JP, Michlikova S, Dinér P, et al. Selective inhibition of RET mediated cell proliferation in vitro by the kinase inhibitor SPP86. BMC Cancer, 2014, 14:853.
40. Placzkowski KA, Reddi HV, Grebe SK, et al. The role of the PAX8/PPARgamma fusion oncogene in thyroid cancer. PPAR Res, 2008, 2008:672829.
41. Uitdehaag JC, de Roos JA, van Doornmalen AM,et al. Selective targeting of CTNBB1-, KRAS- or MYC-driven cell growth by combinations of existing drugs. PLoS One, 2015, 10(5):e0125021.
42. Safa AR, Saadatzadeh MR, Cohen-Gadol AA, et al. Glioblastoma stem cells (GSCs) epigenetic plasticity and interconversion between differentiated non-GSCs and GSCs. Genes Dis, 2015, 2(2):152-163.

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